The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene

dCD38 is a leukocyte activation antigen and ectoenzyme [NAD(P)(+) glycohydr olase; EC 3.2.2.6] involved in numerous immune functions. The human CD38 ge ne is complex [eight exons, >80 kilobases (kb) long] located on Chromosome 4p15, and part of the eukaryotic NAD(+) glycohydrolase/ADP-ribosyl cyclase gene family. Because of the increasing relevance of the CD38 molecule in th e host immune response to infectious, tumoral, and metabolic diseases, we i nvestigated the genetic variability and linkage of the human CD38 locus. We report that (1) the restriction endonuclease Pvu II identifies a bi-alleli c polymorphism here defined as formed by the alleles CD38*A (12 kb) and CD3 8*B (9/2.5 kb); (2) their frequency in the healthy Italian Caucasian popula tion is 14% and 86%, respectively; (3) the polymorphic Pvu II site is locat ed at the 5' end of the first intron of the CD38 gene; (4) in conjunction w ith the polymorphic site, we identified a 900 base pair CPG island associat ed with the CD38 gene, with two potential Spl binding sites; (5) the CpG is land may play a role in the regulation of CD38 expression and is hypomethyl ated in various cell lines; (6) by pulsed-field gel electrophoresis we show that,CD38 and its paralogue, the bone-marrow stromal cell antigen BST-I (C D157), map to the same 800 kb Avi II fragment, indieating that the two huma n ecto-NADase genes are closely linked.